HUT71624A - Optically active alkylammonium(amino-3phenyl)-1ethanesulfonate derivatives, preparation and use thereof - Google Patents

Abstract

PCT No. PCT/FR93/00849 Sec. 371 Date Mar. 10, 1995 Sec. 102(e) Date Mar. 10, 1995 PCT Filed Sep. 6, 1993 PCT Pub. No. WO94/06760 PCT Pub. Date Mar. 31, 1994.This invention relates to levogyral isomers of alkylammonium (amino-3 phenyl)-1 ethanesulphonate derivatives of formula (I) in which R+ denotes a tetraalkylammonium or trialkylphenylalkylammonium residue. The invention also concerns the preparation and use of said derivatives.

Description

The present invention relates to (alkylammonium) - [1- (3-aminophenyl) ethanesulfonate] derivatives of formula (I) wherein R ⁺ is (tetraalkylammonium) or [trialkyl- (phenyl) alkylammonium] cationic, isomeric optically active isomers, a process for their preparation and their use as intermediates for the preparation of cholecystokinin (CCK) and gastrin antagonist compounds.

For the purposes of the present invention, the above and the following definitions refer to a straight or branched alkyl group having from 1 to 4 carbon atoms, preferably butyl.

The compounds of formula (I) (left-rotating optical isomers) can be prepared by the following procedure:

a) (RS) -1- (1-Bromoethyl) -3-nitrobenzene is reacted with an alkali metal sulfite and optionally converted to the potassium salt to give (RS) -Potassium [ 1- (3-nitrophenyl) ethanesulfonate] is obtained,

b) converting the potassium salt obtained in step a) into a mixture of benzylquininium [1- (3-nitrophenyl) ethanesulfonate] forms A and B, separating form A and recovering a mixture enriched in form B,

c) a mixture of the benzylquininium salt rich in form B obtained in step b) to potassium [1- (3-nitrophenyl) ethanesulfonate] followed by phenylglycinol [1- (3-nitrophenyl) ethanesulfonate ] To form B and finally to (tetraalkylammonium) or [trialkyl (phenylalkyl) ammonium] - [1- (3-nitrophenyl) ethanesulfonate] (left-rotating optical isomer),

d) reducing the product of step c) to a compound of formula I (left-turning optical isomer).

• ·

It is particularly advantageous to carry out step a) in an aqueous solution at a temperature of 50 ° C to 100 ° C, preferably 80 ° C.

The alkali metal sulfite is preferably sodium or potassium sulfite.

In a preferred embodiment, the product is obtained by further converting it into the (tetraalkylammonium) or [trialkyl (phenylalkyl) ammonium] salt into the potassium salt.

Step b) is preferably carried out mainly in the presence of chloride in the presence of an aqueous medium at a temperature in the region of 20 ° C.

According to step c), it is formed with butanesulfonate), isolated and then with (N-benzylquininium) halide, and finally potassium dihydrogen phosphate at a temperature of 10 to 30 ° C, preferably the potassium salt is prepared in an inert solvent, for example in acetone at a temperature of from 10 ° C to 30 ° C, preferably at 20 ° C.

According to step c), the phenylglycinol salt is prepared with (R) - (-) - phenylglycinol in the presence of an acid, for example hydrochloric acid, in an aqueous medium at a temperature between 10 ° C and 30 ° C, preferably at 20 ° C.

The phenylglycinol salt is then converted to the compound of formula (I) using a (tetraalkylammonium) or [trialkyl (phenylalkyl) ammonium] salt, which is preferably hydrogen sulfate; the conversion is carried out in an aqueous medium at a temperature between 10 ° C and 30 ° C, preferably at 20 ° C.

The reduction of step d) is generally carried out under pressure in a hydrogen atmosphere in the presence of a hydrogenation catalyst such as palladium, in an inert solvent, an alcohol (e.g. ethanol).

At temperatures around 25 ° C.

Hydrogen pressure of 100 kPa is preferred.

rotating optical isomers) are particularly valuable as compounds of the general formula - wherein

THE)

A group of the formula -CH2-CO-NR1R2 wherein ^{R1 is} optionally substituted with one or more halogen atoms, alkyl, alkoxy, polyfluoroalkyl, nitro, alkylthio, alkoxycarbonyl, carboxy, acylamino, methylenedioxy, polyfluoroalkoxy, trifluoromethylthio, phenoxy, phenyl, benzyl, phenylamino and / or

CONR3R4 - in which

R3 and R4 may be the same or different and are hydrogen, alkyl, phenyl optionally substituted with one or more halogen, alkyl, alkoxy and / or alkylthio, indanal, cycloalkylalkyl, cycloalkyl, phenylalkyl , or R3 and R4 together with the nitrogen atom to which they are attached,

A saturated or unsaturated, mono- or polycyclic heterocycle containing from 4 to 9 carbon atoms and one or more heteroatoms (O, N, S) may be substituted by alkoxy, alkoxycarbonyl, dialkylcarbamoyl and / or phenyl, or by a carbon atom of the heterocycle a 4- to 5-membered moiety optionally bonded to a spiromonocycle containing one or more alkyl, optionally one or more heteroatoms (O, S, N) - substituted phenyl, b) pyridyl, c) isoquinolyl, d) quinolyl, e. ) quinoxalinyl, which heterocycles may be optionally substituted with one or more alkyl, phenyl and / or halogen atoms, f) alkyl, g) phenylalkyl, h) naphthyl, i) 5,6,7,8-tetrahydronaphthyl; group,

j) 1,2,3,4-tetrahydronaphthyl, k) alkoxycarbonylalkyl or 1) cycloalkyl;

R ₂ is -CH (R 5) -CO-R 9 wherein

R5 is hydrogen or phenyl substituted with alkyl, alkoxycarbonyl or optionally substituted with one or more halogen, alkyl, alkoxy, alkylthio, nitro and / or amino groups; and

R8 is alkoxy, cycloalkoxy optionally substituted with at least one alkyl group, cycloalkylalkoxy, phenylalkoxy, (polyfluoroalkoxy) cinnamyloxy, or -NR3R4; obsession

B) a group of the formula (a) in which

R is methylene, ethylene, S0, 3Ο ^_ _2, CHOH, or sulfur; and

R7 is pyridyl optionally substituted by one or more alkyl groups, furyl optionally substituted by one or more alkyl groups, thienyl group optionally substituted by one or more alkyl groups, quinolyl group optionally substituted by one or more alkyl groups, optionally a naphthyl group optionally substituted by one or more alkyl groups. or indolyl substituted with multiple alkyl groups, or optionally with halogen, alkyl, alkoxy, hydroxy, nitro, amino, monoalkylamino, dialkylamino, alkoxycarbonyl, -CO-NR] -] Phenyl substituted with R ₃ 2, -NH-CO-CH 8, trifluoromethyl and / or trifluoromethoxy;

and ^r8 is hydrogen; or is methylene; and ^R 7 is hydrogen; j and ^r 8 of colorless phenyl; or save j

CHR 1 - 3; and ^R7 and R8 are each hydrogen;

R8 is alkoxycarbonyl, cycloalkoxycarbonyl, cycloalkylalkoxycarbonyl, -CONR14R15, or phenyl optionally substituted with one or more alkyl, alkoxy and / or hydroxy groups;

^R 10 is hydrogen or alkyl;

^r 13 is phenyl;

^R n is hydrogen, or phenyl, optionally substituted with one or more halogen, alkyl, alkoxy, and / or alkylthio groups, alkyl, phenylalkyl;

^r 12 is alkyl, phenylalkyl, or phenyl optionally substituted with one or more halogen, alkyl, alkoxy and / or alkylthio groups;

or ^R ii and R 12 together with ^the nitrogen atom to which they are attached,

Form a saturated or unsaturated monocyclic or polycyclic heterocycle containing from 4 to 9 carbon atoms and one or more heteroatoms (O, N) optionally substituted with one or more alkyl groups;

^R 14 is hydrogen, alkyl, cycloalkylalkyl, cycloalkyl, phenylalkyl, or optionally with one or more halogen, alkyl, alkoxy and / or alkyl

phenyl substituted with thio;

^r 15 is alkyl, cycloalkylalkyl, cycloalkyl, phenylalkyl, or phenyl optionally substituted with one or more halogen, alkyl, alkoxy and / or alkylthio groups; or ^R 14 and R] _5 together with the nitrogen atom to which they are attached,

They form a saturated or unsaturated, mono- or polycyclic heterocycle containing from 4 to 9 carbon atoms and one or more heteroatoms (O, N, S) optionally substituted with one or more alkyl groups; obsession

C) a group of formula (b) in which

R16-6 is hydrogen, halogen, alkyl, alkylthio, nitro, hydroxy or cyano;

R17-7 is alkyl or -CH (R5) -CO-R8;

R 1 -g is pyridyl or phenyl optionally substituted with one or more halogen, alkyl, alkoxy, hydroxy, carboxy and / or nitro groups - <

Intermediates for the preparation of the enantiomers.

In the compounds of formula II, alkyl and alkoxy groups and alkyl and alkoxy groups are preferably straight or branched alkyl and alkoxy groups having 1 to 4 carbon atoms, preferably cycloalkyl groups and units.

C3-6 cycloalkyl groups, preferably acyl groups having 2 to 4 carbon atoms.

The above compounds are disclosed in WO91 / 12264, WO91 / 13907, WO91 / 13874, FR9108675 and FR9112481 as cholecystokinin and gastrin antagonists.

can be prepared by reacting a compound of formula (I) with a compound of formula (III) wherein Y is as defined in compound (II).

usually in an inert solvent (e.g. tetrahydrofuran, dimethylformamide), a chlorinated solvent, an aromatic solvent (e.g., benzene, toluene) at a temperature between 20 ° C and the boiling point of the solvent.

The compounds of formula (III) may be prepared according to the methods described in WO91 / 12264, WO91 / 13907, WO91 / 13874, FR9108675 and FR9U2481.

. example:

(a) (RS) -Potassium [1- (3-nitrophenyl) ethanesulfonate]

To a solution of 20.8 g of sodium sulfite in 260 ml of water

(RS) -1- (1-Bromoethyl) -3-nitrobenzene (25.3 g) was added. The reaction mixture was stirred at 80 ° C for 5 hours, then cooled to about 25 ° C and poured into 2.5 L of potassium dihydrogen phosphate solution (2.5 L). 40 g (tetrabutylammonium) bisulfate are added and the mixture is added three times.

It is extracted with 500 ml of dichloromethane. The combined organic layers were washed with water (2 x 500 mL), dried over magnesium sulfate and evaporated to dryness under reduced pressure (2.7 kPa) at 40 ° C. The resulting oily residue was dissolved in acetone (65 mL) and a solution of potassium (nonafluorobutanesulfonate) (34 g) in acetone (75 mL) was added. The precipitated product is recovered from the solution by filtration, washed three times with 50 ml of diisopropyl ether and air-dried. This gives 22.4 g of (RS) potassium [1- (3-nitrophenyl) ethanesulfonate], m.p.> 260 DEG C., which is used as such in the subsequent steps of the synthesis.

1 HNMR Spectrum: (200 MHz; DMSO-dg) δ (ppm):

1 50 [d, J = 7Hz, 3H: -CH (CH 3) -] 3 93 [q, J = 7Hz, 1H -CH (CH 3) -] 7 59 [t, J = 8Hz, 1H -CgH ₄ (-H5)] 7 83 [d, J = 8Hz, 1H: -CgH ₄ (-H 6)]

8.10 [broad d, J = 8 Hz, 1H: ₄ -CgH (-H 4)]

8.26 [br s, 1H -CgH ₄ (H2)]

(R.S) -1- (1-Bromoethyl) -3-nitrobenzene may be prepared according to the method of E. Felder et al., J. Med. Chem., 13, 559 (1970).

b) (N-Benzylquininium) [1- (3-nitrophenyl) ethanesulfonate],

Mixture of A and B forms

To a solution of (RS) potassium [1- (3-nitrophenyl) ethanesulfonate] (17.2 g) in water (400 ml) was added 87 g of potassium dihydrogen phosphate and 32.4 g of N-benzylquininium chloride. The mixture was extracted with dichloromethane (2 x 300 mL). The combined organic layers were washed with water (2 x 200 mL), dried over magnesium sulfate, and under reduced pressure (2.7 kPa).

Evaporate to dryness at 40 ° C.

The resulting foam was a residue

Dissolve in 0 ml of isopropyl alcohol at reflux. After cooling, the precipitated crystals were filtered off and washed with isopropyl alcohol (2 x 15 mL). It was then successively made first with 350 ml and then with 500 ml of isopropyl alcohol

15.6 g (N-benzylquininium) - [1- (3-nitro-phenyl) -ethanesulfonate]

The form is obtained with a melting point of about 110 ° C. [α] ²⁰ _D = -151.3 ° ± 1.5 (c = 1.0009%, methanol).

The mother liquors of the isopropyl alcohol were combined and concentrated to dryness under reduced pressure (2.7 kPa) at 45 ° C. This gives 25.0 g of a mixture of Form A and Form B (N-benzylquininium) - [1- (3-nitrophenyl) ethanesulfonate] (about 15:85 molar ratio).

(c) (Tetrabutylammonium) - [1- (3-nitrophenyl) ethanesulfonate], optical rotating isomer

To a solution of 10.5 g of (N-benzylquininium) - [1- (3-nitrophenyl) ethanesulfonate] A and B (molar ratio about 15:85) in 16 ml of acetone are added 5.2 g of potassium.

- a solution of nonafluorobutanesulfonate in 12 ml of acetone. The precipitated product is filtered off and dissolved in 9 ml of water. To the mixture was added 8.4 ml of 1M aqueous hydrochloric acid and 1.15 g of (R) - (-) - phenylglycinol. The resulting solution was evaporated to dryness under reduced pressure (2.7 kPa) at 50 ° C. The residue was extracted three times with 15 ml of acetonitrile at reflux. The combined organic phases were concentrated to a volume of about 7 ml. After cooling, the crystals were filtered off and dissolved in 7.5 ml of aqueous 1M sodium hydroxide solution. The resulting solution was washed eight times with 25 mL of diethyl ether, followed by addition of 60 mL of 0.5 M aqueous potassium dihydrogen phosphate solution and 2.3 g of (tetrabutylammonium) hydrogen sulfate. The mixture was extracted with dichloromethane (3 x 30 mL). The combined organic layers were dried over magnesium sulfate and evaporated to dryness under reduced pressure (2.7 kPa) at 40 ° C. In this way, 2.8 g (tetrabutylammonium) - [1- (3-nitrophenyl) ethanesulfonate] of the torsional optical isomer are obtained in the form of an oil which is used as such in the subsequent syntheses.

(d) (Tetrabutylammonium) - [1- (3-aminophenyl) ethanesulfonate], optical rotating isomer:

To a solution of 2.8 g (tetrabutylammonium) - [1- (3-nitrophenyl) ethanesulfonate] of the rotary optical isomer in 50 ml of ethanol was added 0.2 g of 5% palladium on carbon. The suspension is stirred under a hydrogen atmosphere (100 kPa) at a temperature in the region of 25 ° C for 2 hours. The catalyst was removed by filtration and the filtrate was evaporated to dryness under reduced pressure (2.7 kPa) at 40 ° C. This way

2.8 g (tetrabutylammonium) - [1- (3-aminophenyl) ethanesulfonate]

a rotary optical isomer is obtained in the form of an oil which is used as such in further syntheses.

1 HNMR Spectrum: (200 MHz; CDCl 3, Form B)

δ (ppm): 0, 98 (T, J = 7Hz, 12H : butyl-CH3) 1,25- -1, 65 (mt, 16H: butyl-CH ₂ -CH ₂ , CH 3 1, 65 (d, J = 7Hz, 3H: -CH (CH ₃ )] 2, 95 (Mf, 2H: -NH ₂ ) 3, 15 (mt, 8H: - (sorry il) (CH ₂ ) -N <] 3, 91 (Qr J = 7Hz, 1H: -CH (CH ₃ ) -] 6, 50 (d, wide, J = 8 Hz, 1H: -CgH ₄ (H4)] 6, 85 (d, J = 8Hz, 1H: -C ₆ H ₄ (H ₆ )] 6.86 [s s broad, 1H: -C ₆ H ₄ (H ₂ )] 7:00 (t, J = 8Hz, 1H: -C ₆ H ₄ (H ₅ ) J

APPLICATION EXAMPLE

To a solution of 2.1 g of 2- (2 - ((1-imidazolyl) carboxamido) -N- (3-methoxyphenyl) acetamido} -N-methyl-N-phenylacetamide in 130 ml of toluene (tetrabutylammonium) - [1- (3-amino

-phenyl) -ethanesulfonate] is added to the left-rotating optical isomer. The reaction mixture was refluxed for 5 hours and then concentrated to dryness under reduced pressure (2.7 kPa) at 45 ° C. The residue was dissolved in dichloromethane (100 mL) and the resulting solution was washed with 2M aqueous hydrochloric acid (50 mL) and water (2 x 50 mL). The organic phase was dried over magnesium sulfate and evaporated to dryness under reduced pressure (2.7 kPa) at 40 ° C. The crude product obtained is stirred in 50 ml of diisopropyl ether for 30 minutes. The precipitated product is filtered off and dissolved in 6 ml of acetone. A solution of potassium (nonafluorobutanesulfonate) (1.2 g) in acetone (3 mL) was added followed by diisopropyl ether (5 mL). The excellent sticky product was isolated and stirred for one hour in a mixture of acetone / diisopropylether (12 ml, 50:50 by volume). The insoluble product is filtered off, washed twice with 5 ml of acetone / diisopropyl ether (50:50 by volume) and four times with 5 ml of diisopropyl ether and air dried. In this way, 1.55 g of (-) - potassium [1- (3- {3- [N- (3-methoxyphenyl) -N- (N-methyl-N-phenylcarbamoylmethyl) carbamoyl) -methyl] -ureido} -phenyl) -ethanesulfonate], m.p. 180 ° C.

[α] D = -5.0 ° ± 5.5 (c = 0.888%, methanol).

¹ HNMR Spectrum: (300 MHz; DMSO-dg, (-) form)

Ö (ppm):

1.43 [d, J = 7Hz, 3H: -CH (CH ₃ ) -]

3.18 [s broad, 3H: -N (CH ₃ ) -]

3, 60 [mt, 1H: CH _(CH3) -]

3.65 [broad d, J = 5 Hz, 2H: --CO _(CH2) NH-]

3.79 (s, 3H: _OCH3)

4.09 [unresolved complex, 2H: --CO _(CH2) N <]

6.28 [t broad, J = 5Hz, 1H: -NH-]

6.86 [d, J = 7.5 Hz, 1H: -C6H4 (-H4) N- (3-methoxyphenyl)]

6.95-7.15 [mt, 4H aromatic]

7.17 [(s broad, 1H: -CgH4 (-H2) N- (3-methoxyphenyl)]

7.30-7.50 (mt, 11H: aromatic)

8.80 (s broad, 1H: -CO-NH-Ar).

2- (2 - ((1-imidazolyl) carboxamido) -N- (3-methoxyphenyl) acetamido} -N-methyl-N-phenylacetamide can be prepared as follows: 3 g of N, N'- To a solution of carbonyldiimidazole in 30 ml of anhydrous tetrahydrofuran is added a solution of 3.1 g of 2- [2-amino-N- (3-methoxyphenyl) acetamido] -N-methyl-N-phenylacetamide in anhydrous tetrahydrofuran. After stirring for 16 hours at a temperature in the region of 25 DEG C., the mixture is evaporated to dryness under reduced pressure (2.7 kPa) and at 40 DEG C. The residue is dissolved in 50 ml of ethyl acetate and the resulting solution is washed four times with 30 ml of water. dried over sulfur and evaporated to dryness under reduced pressure (2.7 kPa) at 40 DEG C. After recrystallization from ethyl acetate, 3.5 g of 2- (2- (

-imidazolyl) -carboxamido] -N- (3-methoxyphenyl) acetamido} -N-methyl-N-phenylacetamide, m.p. 146 ° C.

2- [2-Amino-N- (3-methoxyphenyl) acetamido] -N-methyl-N-phenylacetamide was prepared as follows: 5.5 g of 2- [N- (3-methoxy) To a solution of phenyl) -2-phthalimidoacetamido] -N-methyl-N-phenylacetamide in methanol (1.3 g) was added hydrazine hydrate. The reaction mixture was stirred and refluxed for 30 minutes, and after cooling, 100 ml of water was added. The mixture was concentrated to about 100 mL, adjusted to pH 9 with 2M aqueous sodium hydroxide solution and extracted with ethyl acetate (2 x 50 mL). The combined organic layers were washed with water (2 x 50 mL), dried over magnesium sulfate and evaporated to dryness under reduced pressure (2.7 kPa) at 40 ° C. In this way, 3.0 g of 2- [amino-N- (3-methoxyphenyl) -acetamido] -N-methyl-N-phenyl was obtained. ·

Acetamide is obtained in the form of an oil which is used as such in further syntheses.

2- [N- (3-methoxyphenyl) -2-phthalimidoacetamido] -N-methyl-N

-phenylacetamide may be prepared as follows: 80.6 g of 2- [N- (3-methoxyphenyl) -2-phthalimidoacetamido] acetic acid 900 ml

To a suspension of 1,2-dichloroethane was added 10 ml of dimethylformamide followed by 30.2 g of oxalyl chloride per hour.

The mixture is stirred at a temperature in the region of 25 ° C for 2 hours and 45 minutes and added. The reaction mixture was stirred at a temperature in the region of 25 ° C for 2 hours and then twice

500 ml water, then

It is washed with 300 ml of a saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, and under reduced pressure (2.7 kPa) and

Evaporate to dryness at 40 ° C. The rest

After stirring for one hour with 0 ml of diisopropyl ether, the insoluble product is filtered off, washed with three times ml of diisopropyl ether and air dried. At this

-phenyl) -2-phthalimidoacetamido] -N-methyl-N-phenylacetamide, mp 137 ° C.

2- [N- (3-Methoxyphenyl) -2-phthalimidoacetamido] -acetic acid can be prepared as follows: 42.0 g of 2- [N- (3-methoxyphenyl) -2-phthalimidoacetamido]. To a solution of the acetic acid tert-butyl ester in 500 mL of dichloromethane was added 74.0 g of trifluoroacetic acid. The resulting solution was refluxed for 5 hours and then evaporated to dryness under reduced pressure (2.7 kPa) and 40 ° C. The residue was stirred for one hour by addition of 100 ml of diisopropyl ether, the insoluble product was filtered off, washed three times with 40 ml of diisopropyl ether and air-dried. In this way, 36 g of 2- [N16

(3-Methoxyphenyl) -2-phthalimidoacetamido] -acetic acid is obtained, m.p. 203 ° C.

The 2- [N- (3-methoxyphenyl) -2-phthalimidoacetamido] acetic acid tert-butyl ester can be prepared as follows:

- (3-methoxy-phenyl) -2-phthalimido-acetamide

To a solution of 1000 ml of anhydrous tetrahydrofuran is added a solution of 14.9 ml of sodium hydrate in a minute. The reaction mixture was stirred at a temperature in the region of 20 ° C for 1 hour to 0 minutes

72.7 g of bromoacetic acid tert-butyl and zter are added. The reaction mixture was stirred at a temperature in the region of 25 ° C for 16 hours, then carefully hydrolysed by the addition of 50 ml of water and then evaporated to dryness under reduced pressure. The resulting residue was stirred for one hour by addition of water (400 mL), the insoluble product was filtered off, washed with water (3 x 100 mL) and diisopropyl ether (2 x 100 mL) and air dried. In this way, 82.0 g of 2- [N- (3-methoxy)

-phenyl) -2-phthalimidoacetamido] -acetic acid tert-butyl ester, mp 148 ° C.

To a solution of N- (3-methoxyphenyl) -2-phthalimidoacetamide was prepared by adding 22.0 g of triethylamine to a solution of 26.0 g of 3-methoxyaniline in 200 ml of dichloromethane, and the At a temperature of about 20 ° C, a solution of 2-phthalimidoacetyl chloride (48.0 g) in methylene chloride (300 ml) was added. The mixture was stirred at the indicated temperature for 4 hours and then 800 ml of water were added. The precipitated product is filtered off, washed three times with 100 ml of water and air dried. This gave 65.0 g of N- (3-methoxyphenyl) -2-phthalimididoacetamide, m.p. 171 ° C.

2-Phthalimidoacetyl chloride was prepared by W.Grassmann et al

-Uebbing may be prepared [Chem.

244-247 (1950)].

Claims (17)

A compound of formula (I) (alkylammonium) - [1- (3-amino) patent claims (phenyl) ethanesulfonate] in the formula R ⁺ is the optically-rotating isomer of (tetraalkylammonium) or [trialkyl (phenylalkyl) ammonium] cation. 2. (Tetrabutylammonium) - [1- (3-aminophenyl) ethanesulfonate] (optical rotator isomeric). 3. A process for the preparation of the compounds of formula I according to claim 1, characterized in that: a) Reaction of (RS) -1- (1-bromoethyl) -3-nitrobenzene with an alkali metal sulfite and converting the product to potassium salt with (RS) potassium [1- (3-nitrophenyl) ethanesulfonate ] we win, b) converting the potassium salt obtained in step a) into a mixture of benzylquininium [1- (3-nitrophenyl) ethanesulfonate] forms A and B, separating form A and obtaining the mixture enriched in form B, c) converting the benzylquininium salt enriched in form B obtained in step b) into the sulfonate] form B and finally (tetraalkylammonium) or [trialkyl (phenylalkyl) ammonium] - [1- (3-nitrophenyl) ethanesulfonate] (torsional optical isomer), d) reducing the product of step c) to the left-rotating optical isomer of a compound of formula (I). • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · A process according to claim 3, characterized in that performing step a) in aqueous solution, 50 ° C to 100 ° C, characterized in that: The method of claim 4, 6. The process according to any one of claims 1 to 3, wherein the reagent is sodium or potassium sulfite. 7. Process according to any one of claims 1 to 4, characterized in that the product is recovered in the form of (tetraalkylammonium) or of [trialkyl (phenylalkyl) ammonium] salt. 8. Referring to FIGS. Process according to any one of claims 1 to 3, characterized in that step b) is carried out using an N-benzylquinium halide in an aqueous medium in the presence of potassium dihydrogen phosphate at a temperature of from 10 ° C to 30 ° C. 9. A process according to claim 8 wherein the reagent is N-benzylquininium chloride. 10. Referring to FIGS. Process according to any one of claims 1 to 3, characterized in that the potassium salt of step c) is prepared using potassium (nonafluorobutanesulphonate) in an inert solvent at a temperature between 10 ° C and 30 ° C. 11. A 3-10. Process according to any one of claims 1 to 3, characterized in that in step c) the phenylglycinol salt is prepared with (R) - (-) - phenylglycinol in an aqueous medium in the presence of an acid at a temperature of from 10 ° C to 30 ° C. 12. A 3-11. Process according to any one of claims 1 to 3, characterized in that in step c) the conversion of the (alkylammonium) - or [trialkyl (phenylalkyl) ammonium] salt into a (tetraalkylammonium) - or [trialkyl (phenylalkyl) ) -ammonium] -salt se- • · · · · ························································································································ed. 13. The process according to claim 12, wherein (tetraalkylammonium) or ammonium bisulfate is used. 14. A 3-13. A process according to any one of claims 1 to 3, characterized in that the hydrogenation is carried out in a hydrogen atmosphere under pressure in the presence of a hydrogenation catalyst in an inert solvent at a temperature in the region of 25 ° C. 15th The process of claim 14, wherein a hydrogen pressure of 100 kPa is used. 16th The process according to claim 3, wherein (tetrabutylammonium) - [ 1- (3-aminophenyl) ethanesulfonate] for the production of a rotary optic isomer. 17. A compound according to claim 1 having the formula: wherein THE) -CH2-CO-NR1R2 wherein ^{R1 is} optionally substituted with one or more halogen, alkyl, alkoxy, polyfluoroalkyl, nitro, alkylthioalkoxycarbonyl, carboxy, acylamino, methylene- dioxipolifluoroalkoxy, trifluoromethylthio, phenoxy, phenylbenzyl, phenylamino and / or A phenyl group represented by the formula CONR3R4 - in which hydrogen, alkyl, optionally substituted by one or more halogen, alkyl, alkoxy and / or alkylthio, R3 and R4 may be the same or different and have the meanings: indanyl, cycloalkylalkyl, cycloalkyl, phenyl or an alkyl group R3 and R4 together with the nitrogen atom to which they are attached, They form a saturated or unsaturated monocyclic or polycyclic heterocycle containing from 4 to 9 carbon atoms and one or more heteroatoms (O, N, S) optionally containing one or more alkyl, alkoxy, alkoxycarbonyl, dialkylcarbamoyl and / or phenyl may be substituted, or a 4- to 5-membered spiromonocycle containing one or more heteroatoms (O, S, N) may be attached to a carbon atom of a heterocycle - substituted phenyl, b) pyridyl, c) isoquinolyl, d) quinolyl, e) quinoxalinyl - which heterocycles may be optionally substituted with one or more alkyl, phenyl and / or halogen atoms - f) alkyl, g) phenylalkyl, h) naphthyl, i) 5, 6, 7, 8-tetrahydronaphthyl, j) 1,2,3,4-tetrahydronaphthyl, k) alkoxycarbonylalkyl or 1) cycloalkyl; R ₂ is -CH (R 5) -CO-R 9 in which R5 is hydrogen or phenyl substituted with alkyl, alkoxycarbonyl, or optionally substituted with one or more halogen, alkyl, alkoxy, alkylthio, nitro and / or amino groups; and Rg is alkoxy, optionally at least one • · • · · * alkyl-substituted cycloalkoxy, cycloalkylalkoxy, phenylalkoxy, (polyfluoroalkoxy) -cinnamyl-χχί, or -NR3R4; obsession B) a group of the general formula (a) in which R is methylene, ethylene, S0, S02 ^-, CHOH, or sulfur; and R7 is pyridyl optionally substituted by one or more alkyl groups, furyl optionally substituted by one or more alkyl groups, thienyl group optionally substituted by one or more alkyl groups, quinolyl group optionally substituted by one or more alkyl groups, optionally a naphthyl group optionally substituted by one or more alkyl groups. or indolyl substituted with multiple alkyl groups or optionally substituted with halogen, alkyl, alkoxy, hydroxy, nitro, amino, monoalkylamino, dialkylamino, alkoxycarbonyl, -CO-NR3] -R1-2. phenyl substituted with -NH-CO-CH8, trifluoromethyl and / or trifluoromethoxy; and Rg is hydrogen; obsession R is methylene; and R7 is hydrogen; and Rg is phenyl; obsession R is -CHR3-3-; and R7 and R8 are each hydrogen; R 8 is alkoxycarbonyl, cycloalkoxycarbonyl, cyclo; Alkylalkoxycarbonyl, -CONR14R15 or phenyl optionally substituted with one or more alkyl, alkoxy and / or hydroxy groups; R ₁₀ is hydrogen or alkyl; R 13 is phenyl; R 4 is hydrogen or phenyl substituted with alkyl, phenylalkyl or optionally substituted with one or more halogen, alkyl, alkoxy and / or alkylthio; ^r 12 is alkyl, phenylalkyl, or phenyl optionally substituted with one or more halogen, alkyl, alkoxy and / or alkylthio groups; obsession R ^] _ and Rj_2 together with the nitrogen atom to which they are attached, Form a saturated or unsaturated, monocyclic or polycyclic heterocycle containing from 4 to 9 carbon atoms and one or more heteroatoms (O, N) optionally substituted with one or more alkyl groups; R 1-4 is hydrogen, alkyl, cycloalkylalkyl, cycloalkyl, phenylalkyl, or phenyl optionally substituted with one or more halogen, alkyl, alkoxy and / or alkylthio groups; R1-5 is alkyl, cycloalkylalkyl, cycloalkyl, phenylalkyl, or phenyl optionally substituted with one or more halogen, alkyl, alkoxy and / or alkylthio groups; obsession R] _4 and R] _5, together with the nitrogen atom to which they are attached, · V · · · · · · · · · · · · They form a saturated or unsaturated, mono- or polycyclic heterocycle containing from 4 to 9 carbon atoms and one or more heteroatoms (O, N, S) optionally substituted with one or more alkyl groups; obsession C) a group of formula (b) in which R 1g is hydrogen, halogen, alkyl, alkylthio, nitro, hydroxy or cyano; R 17 is alkyl or -CH (R 5) -CO-R 8; R8 is an optionally substituted enantiomer of one or more halogen, alkyl, alkoxy, hydroxy, carboxy and / or nitro substituted pyridyl or phenyl groups.